tbuckley/cabot-search huggingface dataset:
Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial)
Authors: Aviël Ragamin, Renske Schappin, Marlies de Graaf, Ron A Tupker, Karin B Fieten, Minke M F van Mierlo, Madelon B Bronner, Geertruida L E Romeijn, Manon M Sloot, Celeste M Boesjes, Lisa P van der Rijst, Bernd W M Arents, Thomas Rustemeyer, Marie L A Schuttelaar, Suzanne G M A Pasmans
Journal: British Journal of Dermatology (2023)

Abstract Background Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. Objectives To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. Methods A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. Results Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3–7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [–0.1, 95% confidence interval (CI) –0.3 to 0.2; P = 0.53] or the silver group (–0.1, 95% CI –0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. Conclusions The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.
Immunological drivers of amyotrophic lateral sclerosis
Authors: Tania F. Gendron, Leonard Petrucelli
Journal: Science Translational Medicine (2023)

Amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease involving complex genetic and environmental factors, is associated with neuroinflammation. Preclinical and clinical studies support immune system involvement in ALS pathogenesis, thereby spurring investigations into potential pathogenic mechanisms, immune response biomarkers, and ALS therapeutics.
Digital biobanks are underutilized in dermatology and create opportunities to reduce the burden of skin disease
Authors: Ghislaine Jumonville, David Hong, Atlas Khan, Andrew DeWan, Suzanne M Leal, Chunhua Weng, Lynn Petukhova
Journal: British Journal of Dermatology (2023)

Digital biobanks that integrate genetic data with health data captured by digital sources are used routinely to discover genes, biomarkers, gene–environment interactions and pharmacogenetic relationships across many clinical areas. There remain many opportunities in dermatology to further use biobank data to increase our knowledge about the genetic architecture of skin disease, to resolve disease mechanisms that can be modulated by medical interventions and to discover genetically derived disease relationships that inform on drug repurposing and adverse events. Such knowledge promises to reduce the global burden of skin disease and facilitates the development of tailored medical care.
Learning CNS immunopathology from therapeutic interventions
Authors: Nicholas Schwab, Heinz Wiendl
Journal: Science Translational Medicine (2023)

Modulation of immune cell trafficking across the blood-brain barrier has not only introduced a therapeutic avenue for multiple sclerosis (MS) but also represents an example of reverse translational medicine. Data from clinical trials of drugs such as natalizumab and fingolimod have revealed the involvement of different compartments in relapsing versus non-relapsing MS immune biology, contributed to our understanding of central nervous system (CNS) immune surveillance, and stimulated new fields of research. Here, we discuss the results of these trials, as well as patient biomaterial-based scientific projects, and how both have informed our understanding of CNS immunopathology.
Identification of diagnosis biomarkers based on the delirium-related genes
Authors: Xing-Long Xiong, Shi-Jie Tang, Jing Shi
Journal: International Journal of Surgery (2023)

Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P. R. China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P. R. China. E-mail address: [email protected] (J. Shi). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Additive Prognostic Value of Left Ventricular Dispersion and Deformation in Patients With Severe Aortic Stenosis
Authors: Nicolas Thellier, Alexandre Altes, Michael Rietz, Aymeric Menet, Jeremy Layec, François Outteryck, Ludovic Appert, Christophe Tribouilloy, Sylvestre Maréchaux
Journal: JACC. Cardiovascular imaging (2023)
Severe Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Cardiomyopathies
Authors: Marie-Louise Meng, Jerome J. Federspiel, Matthew Fuller, Ashley McNeil, Ashraf S. Habib, Johanna Quist-Nelson, Matthew Engelhard, Svati H. Shah, Vijay Krishnamoorthy
Journal: JACC Heart Failure (2023)
Method of primary breast cancer detection and the disease-free interval, adjusting for lead time
Authors: Linda de Munck, Anouk H Eijkelboom, Johannes D M Otten, Mireille J M Broeders, Sabine Siesling
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Little is known about the impact of screen-detected breast cancer compared with clinically detected breast cancer on the disease-free interval (ie, free from locoregional recurrences, distant metastasis, contralateral breast cancer). Moreover, it is thought that most studies overestimate the beneficial effect of screening, as they do not adjust for lead time. We investigated the association between method of breast cancer detection and disease-free interval, taking lead time into account. Methods Women aged 50-76 years, diagnosed with breast cancer between 2005 and 2008 were selected from the Netherlands Cancer Registry. Women diagnosed in 2005 were divided into screen-detected and clinically detected cancer and had a follow-up of 10 years (2005 cohort). Women diagnosed in 2006-2008 were divided into screen-detected, interval, and nonscreen-related cancer and had a follow-up of 5 years (2006-2008 cohort). A previously published method was used to adjust for lead time. Analyses were repeated correcting for confounding variables instead of lead time. Results The 2005 cohort included 6215 women. Women with screen-detected cancer had an improved disease-free interval compared with women with clinically detected cancer (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.68 to 0.87). The 2006-2008 cohort included 15 176 women. Women with screen-detected or interval cancer had an improved disease-free interval compared with women with nonscreen-related cancer (HR = 0.76, 95% CI = 0.66 to 0.88; HR = 0.88, 95% CI = 0.78 to 0.99, respectively). Correcting for confounders instead of lead time did not change associations. Conclusion Women with screen-detected cancer had an improved disease-free interval compared with women with a nonscreen-related or clinically detected cancer, after correction for lead time.
Echocardiography-Based Deep Learning Model to Differentiate Constrictive Pericarditis and Restrictive Cardiomyopathy
Authors: Chieh-Ju Chao, Jiwoong Jeong, Reza Arsanjani, Kihong Kim, Yi-Lin Tsai, Wen-Chung Yu, Juan M. Farina, Ahmed K. Mahmoud, Chadi Ayoub, Martha Grogan, Garvan C. Kane, Imon Banerjee, Jae K. Oh
Journal: JACC. Cardiovascular imaging (2023)
Beremagene geperpavec (B-VEC) gene therapy for the treatment of cutaneous wounds in patients with dystrophic epidermolysis bullosa: a critically appraised research paper
Authors: Brent J Doolan, John A McGrath, Jemima E Mellerio
Journal: British Journal of Dermatology (2023)

Dystrophic epidermolysis bullosa (DEB) is a rare inherited blistering skin disease that causes lifelong, slow-to-heal wounds, which predispose patients to chronic inflammation, scarring and an increased risk of developing squamous cell carcinoma. Management is largely supportive with no approved corrective therapies currently available. We critically appraise the phase III clinical trial reported by Guide et al., investigating the topical application of beremagene geperpavec on cutaneous wounds in DEB.
A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma
Authors: Morgan Groover, Neha Gupta, Emily Granger, Vernon J. Forrester, Emily J. Anstadt, William Su, Lauren Heusinkveld, Anna Chen, John N. Lukens, Ann W. Silk, Allison T. Vidimos, Jonathan D. Schoenfeld, Shlomo A. Koyfman, Emily S. Ruiz
Journal: Journal of the American Academy of Dermatology (2023)
Prevalence of Steatotic Liver Disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017–2020
Authors: Markos Kalligeros, Athanasios Vassilopoulos, Stephanos Vassilopoulos, David W. Victor, Eleftherios Mylonakis, Mazen Noureddin
Journal: Clinical Gastroenterology and Hepatology (2023)
Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer
Authors: Joseph C. Murray, Lavanya Sivapalan, Karlijn Hummelink, Archana Balan, James R. White, Noushin Niknafs, Lamia Rhymee, Gavin Pereira, Nisha Rao, Benny Weksler, Nathan Bahary, Jillian Phallen, Alessandro Leal, David L. Bartlett, Kristen A. Marrone, Jarushka Naidoo, Akul Goel, Benjamin Levy, Samuel Rosner, Christine L. Hann, Susan C. Scott, Josephine Feliciano, Vincent K. Lam, David S. Ettinger, Qing Kay Li, Peter B. Illei, Kim Monkhorst, Robert B. Scharpf, Julie R. Brahmer, Victor E. Velculescu, Ali H. Zaidi, Patrick M. Forde, Valsamo Anagnostou
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Although immunotherapy is the mainstay of therapy for advanced non–small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect—especially in the setting of stable disease—calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE). Experimental Design: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. Results: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE. Conclusions: Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy.
Letter to the Editor: Comparing quantitative MRI technologies in steatotic liver disease
Authors: Naim Alkhouri, Mukesh Harisinghani
Journal: Hepatology (2023)

1Hepatology Division, Arizona Liver Health, Chandler, AZ, USA 2Abdominal Imaging Department, Massachusetts General Hospital, Boston, MA, USA Correspondence Naim Alkhouri, Chief Medical Officer, Arizona Liver Health, Chandler, AZ, 85048. Email: [email protected]
Synapse-specific burst coding sustained by local axonal translation
Authors: Hovy Ho-Wai Wong, Alanna J. Watt, P. Jesper Sjöström
Journal: Neuron (2023)

Neurotransmission in the brain is unreliable, suggesting that high-frequency spike bursts rather than individual spikes carry the neural code. For instance, cortical pyramidal neurons rely on bursts in memory formation. Protein synthesis is another key factor in long-term synaptic plasticity and learning but is widely considered unnecessary for synaptic transmission. Here, however, we show that burst neurotransmission at synapses between neocortical layer 5 pyramidal cells depends on axonal protein synthesis linked to presynaptic NMDA receptors and mTOR. We localized protein synthesis to axons with laser axotomy and puromycylation live imaging. We whole-cell recorded connected neurons to reveal how translation sustained readily releasable vesicle pool size and replenishment rate. We live imaged axons and found sparsely docked RNA granules, suggesting synapse-specific regulation. In agreement, translation boosted neurotransmission onto excitatory but not inhibitory basket or Martinotti cells. Local axonal mRNA translation is thus a hitherto unappreciated principle for sustaining burst coding at specific synapse types.
Intrinsic Subtype and Overall Survival of Patients with Advanced HR+/HER2− Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7
Authors: Aleix Prat, Nadia Solovieff, Fabrice André, Joyce O'Shaughnessy, David A. Cameron, Wolfgang Janni, Gabe S. Sonke, Yoon-Sim Yap, Denise A. Yardley, Ann H. Partridge, Astrid Thuerigen, Juan Pablo Zarate, Agnes Lteif, Fei Su, Lisa A. Carey
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The MONALEESA-2, -3, -7 trials demonstrated statistically significant and clinically meaningful progression-free survival and overall survival (OS) benefits with ribociclib plus endocrine therapy (ET) versus ET alone in hormone receptor–positive, HER2-negative (HR+/HER2−) advanced breast cancer (ABC). Understanding the association of intrinsic subtypes with survival outcomes could potentially guide treatment decisions. Here, we evaluated the association of intrinsic subtypes with OS in MONALEESA-2, -3, -7. Experimental Design: Tumor samples from MONALEESA-2, -3, -7 underwent PAM50-based subtyping. The relationship between subtypes and OS was assessed using univariable and multivariable Cox proportional hazards models. Multivariable models were adjusted for clinical prognostic factors. Results: Overall, 990 tumors (among 2,066 patients) from ribociclib (n = 580) and placebo (n = 410) arms were profiled. Subtype distribution was luminal A, 54.5%; luminal B, 28.0%; HER2-enriched (HER2E) 14.6%; and basal-like, 2.8%; and was consistent across treatment arms. The luminal A subtype had the best OS outcomes in both arms, while basal-like had the worst. Patients with HER2E (HR, 0.60; P = 0.018), luminal B (HR, 0.69; P = 0.023), and luminal A (HR, 0.75; P = 0.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; P = 0.137); however, patient numbers were small (n = 28). Conclusions: The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest dataset in HR+/HER2− ABC). While basal-like subtype did not benefit, a consistent OS benefit was observed with ribociclib added to ET across luminal and HER2E subtypes.
Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial
Authors: Hans Wildiers, Anne Armstrong, Eveline Cuypere, Florence Dalenc, Luc Dirix, Steve Chan, Frederik Marme, Carolina P. Schröder, Jens Huober, Francois P. Duhoux, Peter Vuylsteke, Agnes Jager, Etienne Brain, Sherko Kuemmel, Zsuzsanna Pápai, Catharina Willemien Menke-van der Houven van Oordt, Luca Perjesi, Christian Mueller, Chrystelle Brignone, Frederic Triebel
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2− MBC). Patients and Methods: Women with HR+ HER2– MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers. Results: 114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNγ and CXCL10 levels. Conclusions: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2− MBC.
Impact of Rare Structural Variant Events in Newly Diagnosed Multiple Myeloma
Authors: Monika Chojnacka, Benjamin Diamond, Bachisio Ziccheddu, Even Rustad, Kylee Maclachlan, Marios Papadimitriou, Eileen M. Boyle, Patrick Blaney, Saad Usmani, Gareth Morgan, Ola Landgren, Francesco Maura
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Whole-genome sequencing (WGS) of patients with newly diagnosed multiple myeloma (NDMM) has shown recurrent structural variant (SV) involvement in distinct regions of the genome (i.e., hotspots) and causing recurrent copy-number alterations. Together with canonical immunoglobulin translocations, these SVs are recognized as “recurrent SVs.” More than half of SVs were not involved in recurrent events. The significance of these “rare SVs” has not been previously examined. Experimental Design: In this study, we utilize 752 WGS and 591 RNA sequencing data from patients with NDMM to determine the role of rare SVs in myeloma pathogenesis. Results: Ninety-four percent of patients harbored at least one rare SV event. Rare SVs showed an SV class-specific enrichment within genes and superenhancers associated with outlier gene expression. Furthermore, known myeloma driver genes recurrently impacted by point mutations were dysregulated by rare SVs. Conclusions: Overall, we demonstrate the association of rare SVs with aberrant gene expression supporting a potential driver role in myeloma pathogenesis.
Sensitive MRD Detection from Lymphatic Fluid after Surgery in HPV-Associated Oropharyngeal Cancer
Authors: Noah Earland, Nicholas P. Semenkovich, Ricardo J. Ramirez, Sophie P. Gerndt, Peter K. Harris, Zhuosheng Gu, Andrew I. Hearn, Matthew Inkman, Jeffrey J. Szymanski, Damion Whitfield, Benjamin M. Wahle, Zhongping Xu, Kevin Chen, Irfan Alahi, Gabris Ni, Andrew Chen, Wendy Winckler, Jin Zhang, Aadel A. Chaudhuri, Jose P. Zevallos
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification. Experimental Design: We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS). Results: Postoperative lymph was enriched with cf-HPV compared with plasma (P &amp;lt; 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P &amp;lt; 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (−) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P &amp;lt; 0.0001). Conclusions: Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223